Oligonucleotide Drugs for Transthyretin Amyloidosis

In this issue of the Journal, Adams et al.1 and Benson et al.2 report the results of two randomized, double-blind, controlled trials testing the therapeutic efficacy of two different chemically modified oligonucleotides to treat transthyretin amyloidosis, which is an autosomal dominant hereditary polyneuropathy related to the organ deposition of mutant forms of the transthyretin protein (encoded by mutated TTR) over time. The circulating protein is synthesized predominantly in the liver, but there is also important local production in the eye by retinal pigment epithelial cells and by the choroid plexus epithelium. Transthyretin proteins form a homotetramer; tetramers containing at least . . .